Prognosis In Terms Of Overall Survival Research Articles

Circulating Tumor Cells Prediction in Hormone Receptor Positive HER2-Negative Advanced Breast Cancer: A Retrospective Analysis of the MONARCH 2 Trial.

The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials. Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage IVindolent (pStage IVindolent, <5 predicted CTCs). Prognosis was tested in terms of progression-free-survival (PFS) and overall survival (OS) through Cox regression. Patients classified as predicted pStage IVaggressive and predicted pStage Stage IVindolent were, respectively, 183 (28%) and 461 (72%). After multivariable Cox regression, predicted CTCs were confirmed as independently associated with prognosis in terms of OS, together with ECOG performance status, liver involvement, bone-only disease, and treatment arm. Patients in the pStage Stage IVindolent subgroup treated with abemaciclib experienced the best prognosis both in terms of PFS and OS. The treatment effect of abemaciclib on OS was then explored through subgroup analysis, showing a consistent benefit across all subgroups. This study is the first analysis of CTCs modeling for stage IV disease stratification. These results show the need to expand biomarker profiling in combination with CTCs stratification for improved biomarker-driven drug development.

Prognostic value of preoperative serological biomarkers in patients undergoing cytoreductive surgery for ovarian cancer peritoneal metastases.

Peritoneal metastases of ovarian cancer (PMOC) are common at initial presentation. Cytoreductive surgery (CRS) of curative intent has been proven to be efficient in increasing the overall survival (OS) and the disease-free survival (DFS) of these patients. Nevertheless, CRS is associated with high postoperative morbidity, which makes patient selection a major concern. Appropriate prognostic factors that can predict patient outcomes after surgery are still lacking. Preoperative biomarkers and their ratios have been shown to be predictive of patient prognosis for various solid tumors. We aimed to study their correlation with the prognosis of patients undergoing CRS for PMOC. This retrospective study included patients with PMOC operated by CRS. Preoperative biomarkers and other clinicopathological characteristics were studied to determine their prognostic value in terms OS and DFS. 216 patients were included. Patients with preoperative hemoglobin (Hb) <11.7 g/dL had a poorer prognosis in terms of OS (p=0.0062) and DFS (p=0.0077). Additionally, increased neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) >0.32, and platelet-to-lymphocyte ratio (PLR) >214.5 were associated with worse OS (p=0.022, p=0.0028, and p=0.0018, respectively) and worse DFS (p=0.028, p=0.003, and p=0.019, respectively). Multivariate analysis showed that the variables mentioned above were independent predictive factors for OS and DFS. Preoperative Hb level, NLR, MLR, and PLR are prognostic factors for OS and DFS in PMOC patients operated by curative CRS.

Survival Benefits of Laparoscopic Gastrectomy in Elderly Patients With Gastric Cancer: Focusing on Preoperative Nutritional and Inflammatory Status.

Laparoscopic gastrectomy (LG) may have greater clinical benefits as a less invasive surgery for elderly patients with gastric cancer (GC). Therefore, we aimed to evaluate the survival benefit of LG in elderly patients with GC, especially focusing on preoperative comorbidities, and nutritional and inflammatory status. Data collected from 115 patients aged ≥75 years with primary GC who underwent curative gastrectomy, comprising 58 patients who underwent open gastrectomy (OG) and 57 patients who underwent LG, were retrospectively reviewed (total cohort), and 72 propensity-matched patients (matched cohort) were selected for survival analysis. The aim of the study was to determine short- and long-term outcomes, and the clinical markers to identify a population who may benefit from LG in elderly patients. The complication and mortality rates as a short-term outcome in the total cohort and overall survival (OS) as a long-term outcome in the matched cohort did not differ significantly between the groups. In the total cohort, advanced tumor stage and ≥3 comorbidities were independent factors for poor prognosis in terms of OS [hazard ratio (HR)=3.73, 95% confidence interval (CI)=1.78-7.78, p<0.001 and HR=2.50, 95% CI=1.35-4.61, p<0.01, respectively]. The surgical approach was not an independent risk factor for postoperative complications (grade ≥III) and OS. In subgroup analysis of the total cohort, patients with a neutrophil-lymphocyte ratio (NLR) ≥3 in the LG group demonstrated a trend toward greater OS (HR=0.26, 95% CI=0.10-0.64, interaction p<0.05). LG might offer greater survival benefits than OG in frail patients such as those with high NLR.

Are Thalamic Intrinsic Lesions Operable? No-Man's Land Revisited by the Analysis of a Large Retrospective, Mono-Institutional, Cohort.

Thalamic gliomas represent a heterogeneous subset of deep-seated lesions for which surgical removal is advocated, although clear prognostic factors linked to advantages in performance status or overall survival are still lacking. We reviewed our Institutional Cancer Registry, identifying patients who underwent surgery for thalamic gliomas between 2006 and 2020. Associations between possible prognostic factors such as tumor volume, grade, the extent of resection and performance status (PS), and overall survival (OS) were evaluated using univariate and multivariate survival analyses. We found 56 patients: 31 underwent surgery, and 25 underwent biopsy. Compared to biopsy, surgery resulted positively associated with an increase in the OS (hazard ratio, HR, at multivariate analysis 0.30, 95% confidence interval, CI, 0.12-0.75). Considering the extent of resection (EOR), obtaining GTR/STR appeared to offer an OS advantage in high-grade gliomas (HGG) patients submitted to surgical resection if compared to biopsy, although we did not find statistical significance at multivariate analysis (HR 0.53, 95% CI 0.17-1.59). Patients with a stable 3-month KPS after surgery demonstrated to have a better prognosis in terms of OS if compared to biopsy (multivariate HR 0.17, 95% CI, 0.05-0.59). Age and histological grades were found to be prognostic factors for this condition (p = 0.04 and p = 0.004, respectively, chi-square test). Considering the entire cohort, p53 positivity (univariate HR 2.21, 95% CI 1.01-4.82) and ATRX positivity (univariate HR 2.69, 95% CI 0.92-7.83) resulted associated with a worse prognosis in terms of OS. In this work, we demonstrated that surgery aimed at tumor resection might offer a stronger survival advantage when a stable 3-month KPS after surgery is achieved.

Baseline anemia predicts a poor prognosis in patients with non-small cell lung cancer with epidermal growth factor receptor mutations: a retrospective study

BackgroundAnemia is relatively common in cancer patients, and baseline anemia is associated with poor survival in patients with non-small cell lung cancer (NSCLC). However, there is a lack of large-sample studies of patients with NSCLC with epidermal growth factor receptor (EGFR) mutations.MethodsWe retrospectively analyzed anemia‑related data for patients with NSCLC and EGFR mutations who were admitted to Zhejiang Cancer Hospital from January 2013 to June 2019 and treated with targeted therapy. The patients’ clinicopathological features were evaluated by χ2 tests and the relationships between clinical characteristics and prognosis were investigated using Kaplan–Meier and multivariate Cox regression analyses.ResultsA total of 2,029 patients treated with EGFR-tyrosine kinase inhibitors (TKIs) were finally enrolled in this study, of whom 24.6% had baseline anemia. Patients without baseline anemia had longer median overall survival (OS) than patients with baseline anemia (36.10 vs. 29.10 months, P = 0.001), and patients with grade < 2 anemia had longer median OS than those with grade ≥ 2 anemia (35.00 vs. 25.10 months, P < 0.001). Multivariate analyses identified baseline anemia as a factor predicting a poor prognosis in terms of OS in patients with EGFR mutations.ConclusionsBaseline anemia is a significant factor predicting a poor prognosis in terms of OS in patients with NSCLC and EGFR mutations treated with targeted therapy. A higher grade of baseline anemia may also be related to shorter OS. And a higher risk of EGFR-mutated patients who had received targeted therapy could also be observed.

Value of tumor’s depth and width in predicting survival rate in non-muscle- invasive (pT1) bladder cancer

Background: Bladder cancer is classified according to traditional American Joint Committee on Cancer TNM staging. In the absence of nodal (N stage) or distant metastases (M stage), the depth of tumor invasion (T stage) is the most important determination to be made: whether the tumor is invading into or beyond the lamina propria (muscle-invasive bladder cancer) or not (non- muscle-invasive bladder cancer). This study investigated the association between the cutoff value of tumor depth and width and survival rate in non-muscle- invasive (pT1) bladder cancer. Methods: This was a retrospective cohort design of randomly selected, single- centered study. The subjects were patients with pT1 urothelial carcinoma who were diagnosed on transurethral resection of bladder specimens at a tertiary hospital in West Java, Indonesia. The research sample was taken by consecutive sampling from 2015 to 2019. Results: Sixty-four patients from were included in this study. A tumor depth &gt;2 mm resulted in a hazard ratio (HR) of 1.41 (95% confidence interval [CI], 1.27–3.94; p&lt;0.007), with significant difference. A tumor width &gt;2.4 mm also increased HR significantly (3.27; 95% CI, 1.69–5.87; p&lt;0.006). The presence of lymphovascular invasion (LVI) in patients with bladder cancer resulted in an HR of 3.66 (95% CI, 1.5–4.77; p&lt;0.001), with statistically significant difference in overall survival (OS). Conclusion: Tumor invasion depth, tumor width, and LVI appear to be predictive of poor prognosis in terms of OS in patients with pT1 bladder cancer.

Associations of radiological features of adipose tissues with postoperative complications and overall survival of gastric cancer patients.

To evaluate the associations of the radiological features of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with the postoperative complications and overall survival (OS) of patients undergoing laparoscopic radical gastrectomy for gastric cancer. One hundred forty-two patients underwent laparoscopic radical gastrectomy for gastric cancer from February 2013 to May 2016. The radiological features of SAT and VAT were studied by preoperative computed tomography, and the relationships between the parameters of adipose tissues and the intraoperative and postoperative conditions and OS rate of patients were evaluated. A positive linear correlation was found between VAT area and operation duration, and a negative linear correlation was found between VAT density and intraoperative blood loss (p < 0.05 in both). VAT area was an independent risk factor for postoperative complications. VAT area and VAT density were independent risk factors for OS in gastric cancer. A high VAT area was an independent risk factor for postoperative complications of gastric cancer, whereas a low VAT area and high VAT density were independent risk factors for poor prognosis in terms of OS in gastric cancer. • A large visceral adipose tissue (VAT) area is an unfavourable factor affecting the outcomes of radical gastrectomy for gastric cancer. • Low VAT density may be more likely to cause intraoperative bleeding. • VAT area and VAT density were independent risk factors for the OS of patients with gastric cancer.

Androgen Receptor Activity Is Associated with Worse Survival in Glioblastoma.

Some evidence about the role of the androgen receptor (AR) in pathogenesis of glioblastoma have been reported, but no study has focused on measuring the activity of the AR in GB. Therefore, the aim of this work is to study the role of AR and its activity as prognostic biomarkers in glioblastoma (GB). Molecular and clinical data from The Cancer Genome Atlas database were used. The AR-expression at protein-level was obtained from reversed phase protein array (RPPA) assays. The AR-activity was determined by calculating the AR-score, an index calculated by using the expression (at RNA-level) of 13 androgen-responsive-genes. Univariate and multivariate Cox-regression analyses were performed. Finally, a correlation analysis was conducted between protein expression data and the AR-score. Two-hundred and thirty-three patients were included. RPPA data showed a mean AR abundance of 0.027(Statistical Deviation = 0.38) in GB. The univariate Cox-regression analysis showed that the AR-Score was associated with a worse prognosis (Hazard Ratio (HR) = 1.070) while the AR-expression did not show any relationship with survival (HR = 0.869). The association of the AR-score with worse overall survival (OS) was still significant in the multivariate analysis (HR = 1.054). The highest correlation coefficients between the AR-score and RPPA were identified in a group of proteins involved in apoptotic process regulation. GB patients with a high AR-activity present a worse prognosis in terms of OS. Thus, the activity of the AR may have a pathogenic role in GB. In this regard, the activation of the AR in GB may be associated with a dysregulation of apoptosis.

Proposal for Simplified Endoscopic Standardized Grading of Central Airway Complications After Lung Transplantation According to the Long-Term Prognosis Value of the Current MDS Classification

<h3>Purpose</h3> The MDS classification (<i>i.e.</i> Macroscopic aspect, Diameter, Suture) allows an endoscopic grading of bronchial complications after lung transplantation. We aimed to determine the long-term prognosis value of the MDS airway evaluation after lung transplant and to propose a new organization in prognostic stage of the MDS classification. <h3>Methods</h3> We performed a retrospective monocentric cohort study of the consecutive patients who underwent a single or double lung transplant between the January 2015 and December 2021. We analyzed the prospectively evaluated MDS status at day 7, 28 and 90 after transplantation and the long term follow-up. Analyzed outomes were overall survival (OS), chronic lung allograft dysfunction (CLAD) and airways complications (AC) defined by reoperation or rigid bronchoscopy requirement. <h3>Results</h3> During the study period 221 lung transplants were performed. 437 bronchial anastomoses were analyzed at day 7, 378 at day 28 and 336 at day 90. At day 7, patients with extremely severe and extensive necrosis of the bronchial mucosa (M3d) presented worse OS (p<0.01); While extensive ischemic or necrosis bronchial mucosa (M3c) was associated with AC (p<0.01). At day 28, patients with bronchial mucosa necrosis distal to the anastomosis (M3b, 3c and 3d) presented a worse OS (all p≤0.01) and AC (all p<0,01). At day 90, patients who still presented M3c presented worsened OS (p<0.01) and increased risk of AC (p<0.01). Separate analysis of patients with M3b, c and d (at day 28 and 90) showed similar relationship with OS, CLAD and AC (all p<0.01); as far as patients with M0 and M1 had the same prognosis in terms of OS (all p=NS), CLAD and AC (all p=NS), it was the same for M2 and M3a (all p=NS). Therefore, we have reorganized the MDS classification in 3 stages: G1 for M0/M1 a, b, c, d; G2 for M2 a, d, c, d/M3 a; G3 for M3b, c, d. We have compared the 3 groups of patients with G1 as reference. Stage G3 at day 7 was associated with AC (p<0.05) while at days 28 and 90 it was associated with OS, AC and CLAD (all p<0.05) <h3>Conclusion</h3> The endoscopic MDS grading system can be simplified into 3 groups providing prognostic risk stratification of OS, AC and CLAD development after lung transplantation.

The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study.

Backgrounds/AimsThe goal of the present study was to evaluate the prognostic value of lymph node ratio (LNR) in distal cholangiocarcinoma (DCC) after curative intended surgery.MethodsClinicopathological data of 162 DCC patients who underwent radical intended surgery between 2012 and 2020 were analyzed retrospectively. Prognostic factors related to overall survival (OS) and disease-free survival (DFS) were evaluated.ResultsMedian OS time and DFS time were 41 and 29 months, and 5-year OS rate and DFS rate were 44.7% and 38.1%, respectively. In the univariate analysis, significant prognostic factors for OS were histologic differentiation, American Joint Committee on Cancer (AJCC) stage, positive lymph node count, LNR, R1 resection, and perineural invasion. Preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, infiltrative type, histologic differentiation, AJCC stage, positive lymph node count, LNR, R1 resection, perineural invasion, and lymph-vascular invasion were significant prognostic factors for DFS in the univariate analysis. In the multivariate analysis, histologic differentiation, R1 resection, and LNR were the independent prognostic factors for both OS and DFS. The LNR ≥ 0.2 group had a significantly poor prognosis in terms of OS (hazard ratio, 3.915; p = 0.002) and DFS (hazard ratio, 5.840; p < 0.001).ConclusionsLNR has significant value as a prognostic factor of DCC related to OS and DFS. LNR has the potential to be used as a modified staging system with furthermore studies.

Metaplastic breast cancers and triple-negative breast cancers of no special type: are they prognostically different? A systematic review and meta-analysis.

Metaplastic breast cancer (MBC) and triple-negative (TN) BC of no special type are often confounded with each other in terms of survival and prognosis. In this systematic study and meta-analysis, we evaluated the prognosis of each of these two different diagnoses. We conducted a systematic literature search and review using the MOOSE guidelines, through PUBMED database, the Ovid MEDLINE database, and the ISI Web of Science Citation Index Expanded (SCI Expanded). Overall survival (OS) and disease-free survival (DFS) were the main outcomes considered. Our review eventually selected six independent studies, with a total of more than 59 519 patients. MBC was found to associate with worse OS compared to TNBC of no special type, with a significant 40% increased risk of death [summary hazard ratio (SHR) = 1.40, 95% confidence interval (CI): 1.30-1.50]. We found neither heterogeneity ( I2 = 0%) nor evidence of publication bias ( P = 0.82 and P = 0.49 by Begg's and Egger's test, respectively) between studies. No statistically significant difference was found between MBC and TNBC of no special type in terms of DFS (SHR = 1.17, 95% CI: 0.80-1.71). This study demonstrates that TNBC of no special type and MBC have comparable DFS, although the latter presents a significantly worse prognosis in terms of OS. Despite DFS being similar in both subtypes, this did not result in significant OS benefits, with MBC score being the worse of the two diseases.

Retrospective Analysis of Autologous Stem Cell Transplantation for AL Amyloidosis: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation

Autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with light-chain (AL) amyloidosis, but little is known about it in Asian populations. To investigate the outcome of and prognostic factors for ASCT, we retrospectively analyzed ASCT cases registered to the Transplant Registry Unified Management Program between December 1999 and December 2015, with extra clinical information collected through a secondary survey. The primary endpoint was overall survival (OS). Hematologic response, organ response, and transplantation-related mortality were analyzed as secondary endpoints. The database search identified 330 patients (median age, 57 years; range, 31 to 74), and the secondary survey provided details for the 110 patients (33.3%) included in the study cohort. Fewer than 3 organs were involved in 56.4% of the patients, with cardiac involvement in 57.3%. Performance status (PS) was 0 to 1 in 83.6%. The conditioning melphalan dose was reduced in 54.6%. Overall hematologic response was a partial response or better in 77.6% of the patients and a complete response in 49.3%. The 5-year OS was 70.1%. A PS of 0 to 1 was associated with a significantly better prognosis in terms of OS. Although survival after ASCT for AL amyloidosis improved over time, poor PS and cardiac involvement had negative impacts on prognosis. The early mortality after ASCT was 6.4%. Poor PS and cardiac involvement led to high early mortality. A brain natriuretic peptide (BNP) level of 400 pg/mL was associated with worse OS. Our study has several limitations inherent to a retrospective analysis using a questionnaire. The depth of response and biomarker responses were significantly limited by the degree of missing data. Nonetheless, our data support the importance of careful patient selection for good outcomes of ASCT in patients with AL amyloidosis. In our cohort, poor PS and cardiac involvement had a negative impact on prognosis, and BNP level was a useful prognostic factor.

Preliminary Efficacy Report and Prognosis Analysis of Endoscopic Endonasal Nasopharyngectomy for Recurrent Nasopharyngeal Carcinoma.

Background: Compared with radiotherapy, endoscopic endonasal nasopharyngectomy (EEN) is increasingly used to treat recurrent nasopharyngeal carcinoma (NPC) because of its good prognosis and mild complications. This study aims to investigate the efficacy of EEN in the treatment of recurrent NPC and factors affecting prognosis.Methods: This study included all patients who received EEN for recurrent nasopharyngeal carcinoma from April 2016 to April 2020. All operations were performed in Xiangya Hospital Central South University. The patient's 2-year overall survival (OS) rate, disease-free survival (DFS) rate and significant prognostic factors are reported.Results: There were 38 (67.9%) males and 28 (32.1%) females, with a median age of 43 (range, 24–69 years).43 (76.8%) of the patients in our study were in advanced rT3-rT4 stage and 32 (74.4%) of the patients in the advanced stage had tumor growth closely related to the internal carotid artery (ICA). During a mean follow up period of 44 month (range 1–65 months) post-surgery. The 2-year OS rate was 48.6%, 2-year DFS rate was 42.6%. The 2-year OS rates of rT1-2 and rT3-4 recurrent NPC were 83.9 and 35.6%, respectively. The 2-year DFS rates of rT1-2 and rT3-4 recurrent NPC 76.2 and 56.3%. The advanced T stage were associated with a poor prognosis in terms of OS and DFS.Conclusions: Data indicate that T staging may be an independent prognostic factor for OS and DFS. Through proper preoperative evaluation, EEN is an alternative treatment option for advanced recurrent NPC that ensures a certain level of efficacy and is relatively safe with few complications. However, additional studies with long-term follow-up and a larger sample size are required.

A novel combination score based on early serum tumor markers and neutrophil-to-lymphocyte ratio dynamics predicts response to PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer.

e21095 Background: Serum tumor markers (STM) are viewed as surrogate indicators of tumor burden, and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with the systematic inflammation and immunity status of the host. The present study was designed to evaluate early STM and NLR dynamics as combined biomarkers to predict efficacy and prognosis for advanced non-small cell lung cancer (NSCLC) patients who received immunotherapy with PD-1/PD-L1 inhibitors. Methods: We retrospectively reviewed patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors. Several STM, including carcinoembryonic antigen (CEA), cytokeratin-19 fragments (CYFRA 21–1), neuron specific enolase (NSE), carbohydrate antigen 19–9 (CA19–9), and carbohydrate antigen 125 (CA125), and NLR were routinely measured or calculated at NSCLC diagnosis. Early leading STM and NLR change were evaluated between immunotherapy initiation and the first subsequent restaging. At least 20% decreases of the leading STM were considered as leading STM decrease after immunotherapy. Both pretreatment and posttreatment NLR &lt; 5 were considered as continuous low NLR. A combination score based on the leading STM and NLR dynamics was calculated. The effects of leading STM change, NLR change, and the combination score on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed in a training cohort (n = 79) and confirmed in a validation cohort (n = 35). Results: A total of 120 patients were included in this retrospective cohort study. The median age was 63.0 years and 71.0% was male. Overall, ORR was 20.0%, and median OS and PFS were 6.2 and 4.6 months, respectively. Patients with low combination score had a significantly improved ORR (15/60) compared to those with intermediate (0/11), or high score (0/4) ( P = 0.032). In the training cohort, the combination score was significantly associated with OS ( P &lt; 0.001) and PFS ( P &lt; 0.001) for all patients, as well as for those with stable and progressive disease ( P &lt; 0.001 for OS; P &lt; 0.001 for PFS). This combination score was also further confirmed to stratify patients with different prognosis in terms of OS ( P &lt; 0.001) and PFS ( P &lt; 0.001) in the validation cohort. In a multivariable model, the combination score was an independent indicator for predicting OS ( P &lt; 0.001) and PFS ( P &lt; 0.001). Conclusions: A simple and novel combination score based on early STM and NLR dynamics representing surrogate indicators of tumor burden, and immunity status, respectively, can accurately predict efficacy and prognosis for advanced NSCLC patients with PD-1/PD-L1 blockade.

Characteristics and transplant outcome of myeloid sarcoma: a single-institute study.

We performed a retrospective study describing the characteristics of myeloid sarcoma (MS) and evaluated the outcome of hematopoietic stem cell transplantation (HSCT) in patients with MS. There were 27 patients with de novo isolated MS, 34 with de novo leukemic MS and 13 with secondary leukemic MS in our study. Sixty-three patients received induction chemotherapy. Following induction therapy, 35 patients underwent HSCT, including 10 autogenous HSCT (auto-HSCT) and 25 allogeneic HSCT (allo-HSCT) cases. Compared with intensive chemotherapy only as consolidation treatment, HSCT (auto-/allo-HSCT) significantly improved the overall survival (OS) of MS patients (p < 0.05), while allo-HSCT also improved progression-free survival (PFS, p = 0.032). According to multivariate analysis, poorer prognosis in terms of OS was observed in older patients (p = 0.024, HR = 1.030, 95% CI 1.004-1.057), while HSCT (auto/allo-HSCT) had a favorable impact on OS for patients with MS (auto-HSCT, p = 0.044, HR = 0.201, 95% CI 0.042-0.959; allo-HSCT, p = 0.038, HR = 0.341, 95% CI 0.124-0.943). Extramedullary disease without complete remission (CR) after induction therapy was the sole variable independent of high OS and PFS (p = 0.049, HR = 2.243, 95% CI: 1.005-5.005; p = 0.017, HR = 2.535, 95% CI 1.180-5.448, respectively). The data indicate that HSCT is an effective treatment for patients with MS who have achieved CR of extramedullary disease after induction therapy.

A Novel Four-Gene Prognostic Signature as a Risk Biomarker in Cervical Cancer.

Background Cervical cancer (CC) is a major malignancy affecting women worldwide, with limited treatment options for patients with advanced disease. The aim of this study was to identify novel prognostic biomarkers for CC. Methods RNA-Seq data from four Gene Expression Omnibus datasets (GSE5787, GSE6791, GSE26511, and GSE63514) were used to identify differentially expressed genes (DEGs) between CC and normal cervical tissues. Functional and enrichment analyses of the DEGs were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Oncomine database, Cytoscape software, and Kaplan-Meier survival analyses were used for in-depth screening of hub DEGs. The Cox regression was then used to develop a prognostic signature, which was in turn used to create a nomogram. Results A total of 207 DEGs were identified in the tissue samples, eight of which were prognostically significant in terms of overall survival (OS). Thereafter, a novel four-gene signature consisting of DSG2, MMP1, SPP1, and MCM2 was developed and validated using stepwise Cox analysis. The area under the receiver operating characteristic (ROC) curve (AUC) values were 0.785, 0.609, and 0.686 in the training, verification, and combination groups, respectively. The protein expression levels of the four genes were well validated by the western blotting. Moreover, the nomogram analysis showed that a combination of this four-gene signature plus lymph node metastasis (LNM) status effectively predicted the 1- and 3-year OS probabilities of CC patients with accuracies of 69.01% and 83.93%, respectively. Conclusions We developed a four-gene signature that can accurately predict the prognosis in terms of OS, of CC patients, and could be a valuable tool for designing treatment strategies.

Comparison of the prognosis of primary vs. progressive muscle invasive bladder cancer after radical cystectomy: Results from a large multicenter study

PurposeTo assess whether progressive and primary muscle invasive bladder cancer (MIBC) have different prognosis after radical cystectomy or not. To date only a few data are available on this topic with conflicting results. Further studies on large cohort are needed to clarify these outcomes that may influence bladder cancer management for these patients. Material and methodsA multicentre retrospective study was conducted on patient treated for MIBC at 5 centres between 2005 and 2015 by radical cystectomy. Patients’ outcomes were compared between patients with primary MIBC vs. progressive MIBC subsequent to a history of non-muscle invasive bladder cancer (NMIBC). ResultsA total of 1197 patients were included. Median (IQ) age was 65 (58–72) years and median follow-up was 65 months. Baseline characteristics were similar between the groups as well as the Tumour pT stage, N status and positive surgical margins. Patients with progressive MIBC had worse overall survival (OS) (hazard ratio [HR] 1.36, [95%CI 1.10–1.76]; P = 0.004), cancer specific survival (CSS) (HR 1.41 [1.13–1.78]; P = 0.002), and recurrence-free survival (RFS) (HR 1.21 [1.01–1.49]; P = 0.05). Pathological stage ≥pT3, positive surgical margins, and positive lymph nodes status (pN+) were also found as predictors of OS, CSS, and RFS. ConclusionsOur results suggest that patient having a progressive BC have a worse prognosis in terms of OS, PFS, and CSS than patient with primary disease. These 2 groups may require different management and patients with high risk NMIBC should be assessed properly to avoid progression and be offered early cystectomy.

P-73 Clinical prognostic factors for overall survival and time to progression in RAS-wild type metastatic colorectal cancer treated with anti-EGFR monoclonal antibodies as third or subsequent-line therapy

Survival from metastatic colorectal cancer (mCRC) has improved with the use of anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies. However, one in four patients treated with it as a third or subsequent line therapy will not benefit. This study aims to identify prognostic factors for overall survival (OS) and time to progression (TTP) in Ras-wild type (RAS WT) colorectal cancer treated with anti-EGFR monoclonal antibodies as third or subsequent line therapy. This retrospective analysis included patients with RAS WT mCRC treated with cetuximab or panitumumab as third or subsequent line therapy between 2012 and 2017 at Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology. Multivariate Cox proportional regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and TTP. A total of 162 patients were included in the study. Median age at diagnosis was 65 years, 87 (53,7%) patients were male. Median OS and TTP were 10.9 months and 4.1 months, respectively. Among 134 (83%) pts evaluable for response, there were 35 (26%) partial responses (PRs), 50 (37%) pts with SD and 49 (37%) pts with PD. No differences in OS and TTP were observed between cetuximab and panitumumab. A significantly worse prognosis in terms of OS was observed for patients with peritoneal metastasis (HRs = 2.54, p=0.01). There was also a trend towards worse overall survival in patients with lung metastasis (p= 0.07) and those with elevated serum alkaline phosphatase levels (p= 0.06). Factors associated with shorter TTP were lung metastasis (HRs = 1.63, p=0.02) and ECOG performance status (PS) greater than or equal to 2 (HRs = 2.58, p=0.002). A significantly better prognosis in terms of both OS and TTP was observed for patients with body mass index (BMI) above 25 kg/m2 [HRs = 0.5 (p=0.01) and 0.66 (p=0.049), respectively]. Taking into account the presence of visceral metastases, lung metastases, elevated serum ALKP and BMI<25, we constructed a new prognostic model by combining these prognostic variables in the following way: low-risk group (0 adverse factors); intermediate group (1-2 factors); high-risk group (3-4 factors). Median survival duration for low, intermediate, and high-risk groups were 15.4 months, 11.4 months, and 5.6 months, respectively. Patients from the low-risk group had significantly better survival than those in high-risk group (HR 0,41; CI 95% 0,232-0,711; p=0,002). Anti-EGFR antibodies are effective as the third or subsequent-line therapy in RAS WT mCRC patients. Patients with peritoneal metastasis showed worse prognosis in terms of OS, whereas lung metastasis and ECOG PS ≥2 were associated with shorter TTP. Our novel prognostic model was able to efficiently identify 3 groups of patients with significantly different OS outcomes.

Isolated lymph node recurrence in epithelial ovarian cancer: Recurrence with better prognosis?

IntroductionThe aim of this study was to compare overall survival (OS) between women with isolated lymph node recurrence (ILNR) and those with isolated peritoneal localization of recurrence (ICR), in patients managed for epithelial ovarian cancer. MethodsData from 1508 patients with ovarian cancer were collected retrospectively from1 January 2000 to 31 December 2016, from the FRANCOGYN database, pooling data from 11 centres specialized in ovary treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to define prognostic factors of overall survival. Patients included had a first recurrence defined as ILNR or ICR during their follow up. Results79 patients (5.2 %) presented with ILNR, and 247 (16.4 %) patients had isolated carcinomatosis recurrence. Complete lymphadenectomy was performed more frequently in the ILNR group vs. the ICR group (67.1 % vs. 53.4 %, p = 0.004) and the number of pelvic lymph nodes involved was higher (2.4 vs. 1.1, p = 0.008). The number of involved pelvic LN was an independent predictor of ILNR (OR = 1.231, 95 % CI [1.074–1.412], p = 0.0024). The 3-year and 5-year OS rates in the ILNR group were 85.2 % and 53.7 % respectively, compared to 68.1 % and 46.8 % in patients with ICR. There was no significant difference in terms of OS after initial diagnosis (p = 0.18). 3- year and 5-year OS rates after diagnosis of recurrence were 62.6 % and 15.6 % in the ILNR group, and 44 % and 15.7 % in patients with ICR (p = 0.21). ConclusionILNR does not seem to be associated with a better prognosis in terms of OS.

The MIMIC Study: Prognostic Role and Cutoff Definition of Monocyte-to-Lymphocyte Ratio and Lactate Dehydrogenase Levels in Metastatic Colorectal Cancer.

Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I., 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. High monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR-LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR-LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC.